Inflammatory bowel disease (IBD) is a chronic and debilitating condition of unknown etiology that is characterized by relapsing episodes of ulceration and gastrointestinal inflammation. Continued influx of inflammatory cells to damaged tissue changes tissue metabolism including increased oxygen and nutrient demand and generations of reactive oxygen species (ROS). Methylation inhibition has been shown to exacerbate dextran sodium sulfate (DSS)-induced colitis while folate (which promotes methylation) was protective. Betaine, an essential biochemical molecule of the methionine metabolic cycle, is a potent and safe methyl donor that also promotes methylation reactions. Dietary betaine intake has been shown to significantly suppress ROS generation and lower plasma C-reactive protein, IL-6 and TNF-α levels. Hence, the purpose of this study was to investigate the efficacy of betaine treatment in a mouse model of colitis.Methods:
Male C57Bl/6J mice were used for our study and 2 different experimental protocols were followed. In Experiment I, (prevention study), mice were weighed and then randomly divided into 4 groups to receive sterile water, 3% DSS, 2% betaine or 3% DSS supplemented with 2% betaine in drinking water for a period of 5 days. All mice were given free access to food. Each day, the mice were monitored for weight loss, signs of diarrhea and physiologic stress. At the time of sacrifice, the colon was isolated and transected at the colorectal margin and at the ileocolonic margin. Colon lengths were measured and the tissue was prepared for H&E. Histological examination was performed by a single pathologist (AJL) blinded to the treatment groups using a previously published histological scoring system based on the severity of inflammation (0–3) and linear extent of injury (0%–100%). The scores of the 2 parameters were multiplied and the mean ± SEM was calculated as a measure of the histological disease activity index (DAI). In experiment II (recovery study), all mice were given DSS for 5 days and then half the mice were given 2% betaine in drinking water for up to additional 10 days. Daily monitoring of the mice and sacrificing protocols were exactly as detailed for the prevention study.Results:
We observed severe inflammation and extent of injury in mice given 3% DSS as compared to control or betaine-alone treated mice. However, administering betaine along with DSS revealed a significant decrease in the body weight loss (DSS: −17% ± 0.02; DSS+Betaine: −12% ± 0.02; P < 0.05) compared to control mice. Further, the DAI were also improved by betaine co-treatment (DSS: 45.0 ± 15.9; DSS+Betaine: 12.6 ± 1.6; P < 0.02). In the recovery study (Experiment II), mice given betaine supplemented water had faster weight gain and improved DAI at 6 and 10 days after stopping DSS treatment compared to mice given only water.Conclusions:
We show that treatment with betaine significantly attenuated intestinal inflammation and accelerated tissue healing in a murine model of colitis. Our results suggests that betaine could be an effective supportive therapeutic for the treatment of IBD. The protective effect of betaine could be due to its ability to maintain essential methylation reactions and the epithelial barrier integrity.